MKLs: Co-factors of serum response factor (SRF) in neuronal responses

Serum response factor (SRF) is a major transcription factor that regulates activity-driven gene expression in neurons. Activation of SRF-driven transcription occurs through its interaction with two families of co-factors: ternary complex factor (TCF) and myocardin-related transcription factors (MRTFs). This review focuses on the MRTF family members MKL1 (MAL/MRTF-A/BSAC) and MKL2 (MRTF-B/MAL16). MKLs share several high-homology domains but a low level of sequence identity in the transactivation domain. Both co-activators are expressed in the brain and regulate SRF-dependent gene expression. MKL1 and MKL2 function as major co-activators of SRF function in the developing mouse brain. MKLs inactivation causes ineffective neuronal migration and aberrant neurite outgrowth during development. Moreover, inhibition of MKL1 or MKL2 by short-hairpin RNAs results in a decreased number of dendritic processes and dendritic length. Altogether, MKLs appear to regulate plasticity-related structural changes in neurons.